Journal
BRAIN RESEARCH BULLETIN
Volume 174, Issue -, Pages 11-21Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2021.05.006
Keywords
Ischemic brain injury; NLRP3; Caspase-1 signaling pathway Microglia; Pyroptosis
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The study demonstrated that Dex exerts a protective role against ischemic brain injury by inhibiting microglial pyroptosis through the P2X7R/NLRP3/Caspase-1 pathway. Dex treatment alleviated neurological deficits, reduced brain water content and infarct size in p-MCAO rats. Furthermore, in vitro and in vivo experiments indicated that Dex could enhance cell activity and reduce LDH activity by suppressing the P2X7R/NLRP3/Caspase-1 pathway.
Dexmedetomidine (Dex) has been suggested to exert a protective function in ischemic brain injury. In this study, we aimed to elucidate the intrinsic mechanisms of Dex in regulating microglia pyroptosis in ischemic brain injury via the purinergic 2X7 receptor (P2X7R)/NLRP3/Caspase-1 signaling pathway. First, permanent middle cerebral artery occlusion (p-MCAO) rat model was established, followed by the measurement of behavioral deficit, neuronal injury, the volume of brain edema and the infarct size. Dex treatment was suggested to alleviate the neurological deficits in p-MCAO rats and reduce the brain water content and infarct size. Additionally, rat microglia were cultured in vitro and a model of oxygen and glucose (OGD) was established. Microglia cell activity and ultrastructure were detected. Dex could increase cell activity and reduce LDH activity, partially reversing the changes in cell morphology. Furthermore, the activation of P2X7R/NLRP3/Caspase-1 pathway was tested. The obtained findings indicated Dex suppressed microglial pyroptosis by inhibiting the P2X7R/NLRP3/Caspase-1 pathway. Inhibition of P2X7R or NLRP3 could inhibit Caspase-1 p10 expression, improve cell activity, and reduce LDH activity. The same result was verified in vivo experiments. This study indicated that Dex inhibited microglia pyroptosis by blocking the P2X7R/NLRP3/Caspase-1 pathway, thus playing a protective role against ischemic brain injury.
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